It is proposed to continue studies which are designed to delineate the role of various tetrahydroisoquinoline alkaloids in alcoholism. The studies are now extended to delineate the endogenous formation of these alkaloids, to develop further complex methodologies to study the metabolism of such alkaloids, and to transfer this new expertise to direct studies of human alcoholism. These investigations will focus on two major objectives. It is proposed to utilize newly developed technology to assess endogenous formation of neuroamine-derived alkaloids in experimental animals chronically exposed to ethanol and in human alcoholics. The other major objective is to delineate the pharmacologic properties of these newly identified amine-derived alkaloids.